Methamphetamine (MA) is the fastest growing street drug in the United States. Approximately 10.4 million or 4.3% of the US population have used MA at some time in their lives. Also, 6.2% of high school students are reported using MA at some point in their lives. In South Korea, MA abuse has been the most prevalent form of drug abuse for many decades. Structural, neurochemical, and functional brain imaging studies in adult MA users reported neurobiological deficits in the prefrontal cortex and its potential recovery with abstinence. In contrast, MA exposure in adolescence may impair the normal maturation and pruning of the prefrontal cortex, depending on specific times of the exposure. Our pilot data indicates that adolescent MA abusers (13-18 years old) have a thinning in the prefrontal gray matter and that this deficit correlated inversely with age of onset. In the current proposal, we will conduct a longitudinal follow-up study, baseline, 6-month and 24-month, for early and late onset adolescent MA users using brain magnetic resonance imaging scans for cortical thickness analysis, diffusion tensor imaging for assessing white matter integrity and magnetic resonance spectroscopy for quantifying neuronal viability. Our longitudinal design is likely to provide the information on the 'fixed, progressive, or resilient course from MA-induced neurotoxicities' and 'MA effects on the developing brain.' Second, this multimodal imaging design will provide in-depth knowledge of MA-induced structural and functional brain deficits. Third, the combination of longitudinal and multimodal imaging design provides the information the MA's influence on developmental trajectories of the brain. Our main research hypotheses are 1) MA dependent adolescents will have prefrontal deficits relative to controls, 2) early-onset adolescent MA users will have greater prefrontal deficits than late-onset one, and 3) recovery from abstinence will be only observed in the early-onset but not in the late-onset MA abusers. Exploratory analyses will also assess 1) the association between MA-induced neurotoxicities and neuropsychological dysfunction and 2) the potential combined effects of HIV and MA on the developing brain. We believe that this research proposal is strongly responsive to the International Research Collaboration on Drug Addiction in Program Announcement (PA-07-275) that encourages utilization of unique opportunities that exist abroad and places emphasis on securing foreign matching funds. As is also acknowledged in the 2007 Distinguished International Scientist Awards to our team, our efficient collaboration will contribute to a better understanding of the impact of MA abuse on the developing brain, which will help develop more efficacious prevention and treatment strategies for the fastest growing street drug in the United States. PUBLIC HEALTH RELEVANCE This longitudinal follow-up neuroimaging study for adolescent methamphetamine (MA) dependent subjects will contribute to a better understanding of the impact of MA abuse on the developing brain in adolescence. In particular, we wish to evaluate whether MA use during adolescence is associated with long-term adverse effects on frontal lobe structure and function. This knowledge will help develop more efficacious prevention and treatment strategies for the fastest growing street drug in the United States.